Process for preparing N-phosphonomethylglycinonitrile or derivatives thereof

ABSTRACT

A process for the manufacture of an acid salt of an alkyl ester of N-phosphonomethylglycinonitrile is described which comprises reacting methyleneaminoacetonitrile trimer with a trialkylphosphite. The process is carried out under anhydrous conditions and in the presence of an anhydrous acid and an inert solvent in which methyleneaminoacetonitrile trimer is at least partially soluble and the acid salt of the alkyl ester of N-phosphonomethylglycinonitrile product is substantially insoluble. This is followed by recovering the precipitated acid salt of the alkyl ester of N-phosphonomethylglycinonitrile.

This application was filed under 35 USC 371 and is a continuation of PCTInternational Application No. PCT/GB94/0051, which was filed on Mar. 15,1994.

This application was filed under 35 USC 371 and is a continuation of PCTInternational Application No. PCT/GB94/0051, which was filed on Mar. 15,1994.

The present invention relates to a process for the manufacture ofN-phosphonomethylglycinonitrile or salts and esters thereof.

N-phosphonomethylglycinonitrile is a known compound, useful as aherbicide. It may also be converted by hydrolysis into the commerciallyimportant herbicide N-phosphonomethylglycine.

N-phosphonomethylglycinonitrile is described for example in U.S. Pat.No. 4,221,583. An alternative process for the manufacture ofN-phosphonomethylglycine via the intermediate formation ofN-phosphonomethylglycinonitrile is described in U.S. Pat. No. 3,923,877whilst a related process which is also believed to proceed viaN-phosphonomethylglycinonitrile as an intermediate is described in U.S.Pat. No. 4,415,503.

A process for the preparation of a diaryl ester ofN-phosphonomethylglycinonitrile is disclosed in U.S. Pat. No. 4,083,898,and in EP-A-0068732 there is disclosed a process for the manufacture ofmonoesters and diesters of N-alkyl-substituted amino methyl phosphonicacid using a trisubstituted hexahydro-1,3,5-triazine as startingmaterial.

We have now found that the action of a trialkylphosphite phosphonatingagent on methyleneaminoacetonitrile trimer in the presence of an acidand an inert solvent provides an improved process which is well adaptedto manufacture on a commercial scale and which provides excellent yieldsof N-phosphonomethylglycinonitrile in the form of a salt of its alkylester containing an exceptionally low level of impurities.

According to the present invention there is provided a process for themanufacture of an acid salt of an alkyl ester ofN-phosphonomethylglycinonitrile which comprises reactingmethyleneaminoacetonitrile trimer with a trialkylphosphite underanhydrous conditions and in the presence of an anhydrous acid and aninert solvent in which the methyleneaminoacetonitrile trimer startingmaterial is at least partially soluble and the acid salt of the alkylester of N-phosphonomethylglycinonitrile product is substantiallyinsoluble and thereafter recovering the precipitated acid salt of thealkyl ester of N-phosphonomethylglycinonitrile.

The description methyleneaminoacetonitrile trimer as used herein refersto the compound of formula as shown in Scheme 1 which illustrates theprocess of the present invention. In Scheme 1, the groups R in thetrialkylphosphite (II) represent C₁₋₇ alkyl groups and preferably C₁₋₅alkyl groups and the trialkylphosphite is thus preferably a tri (C₁₋₇alkyl)phosphite or a tri(C₁₋₅ alkyl)phosphite.

The trialkylphosphite is preferably trimethylphosphite,triethylphosphite or tributylphosphite. Trimethylphosphite is a readilyavailable phosphonating agent which is thus a particularly effectivefeedstock for the commercial manufacture ofN-phosphonomethylglycinonitrile. Higher alkyl phosphites such astributylphosphite and tripentylphosphite may provide advantages in termsof commercial production of product as indicated in more detail below.

Suitable anhydrous acids which can be used in the process of the presentinvention and which will form an insoluble salt of the alkyl ester ofN-phosphonomethylglycinonitrile product will occur to those skilled inthe art. Hydrogen halides are especially suitable for use in the processof the present invention. Hydrogen chloride in particular is aneffective and readily available anhydrous acid.

The solvent should be inert in the sense that it is not significantlyattacked under the reaction conditions, and in particular the solventshould be stable against attack by the trialkylphosphite. Suitable inertsolvents in which the methyleneaminoacetonitrile trimer startingmaterial is at least partially soluble and the acid salt of the alkylester of N-phosphonomethylglycinonitrile product is substantiallyinsoluble will occur to those skilled in the art. It is to be understoodthat the methyleneaminoacetonitrile trimer starting material should beat least partially soluble in the inert solvent. By this is meant thatthe methyleneaminoacetonitrile trimer starting material should besufficiently soluble that, even though all the starting material may notbe dissolved at the commencement of the phosphonation reaction,sufficient will be in solution for the phosphonation reaction to start.Thereafter more starting material will dissolve as the reactionprogresses and the starting material in solution is depleted untilsubstantially all the starting material has dissolved by the time thephosphonation reaction is completed. Examples of suitable inert solventsinclude nitriles such as acetonitrile, esters such as ethyl acetate,haloalkanes such as ethylene dichloride and dichloromethane, ketonessuch as metylisobutyl ketone, ethers such as diethyl ether ortetrahydrofuran and halogenated aromatic hydrocarbons such asmonochlorobenzene. Acetonitrile is an especially effective solvent inwhich the methyleneaminoacetonitrile trimer is generally completelysoluble at the concentrations used in the process of the presentinvention.

It is not essential that the acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile product is completely insoluble in thesolvent; it is sufficient that at least a proportion of the acid salt ofthe alkyl ester of N-phosphonomethylglycinonitrile product precipitatesunder the reaction conditions and is recovered accordingly. In general,however the acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile has a very low solubility in themajority of organic solvents and this represents a particular advantageof the process of the present invention.

The reaction conveniently takes place substantially at ambienttemperature although higher or lower temperatures, for exampletemperatures in the range from -50° C. to 200° C., for example, from-10° C. to 50° C. may be used if desired. Heat may be generated duringthe course of the reaction and the reaction may if desired be cooled tomaintain the temperature substantially at the preferred value, forexample, at ambient or slightly above.

When gaseous hydrogen chloride is used as the acid, it may either bepassed directly into the reaction mixture or may be added to thereaction mixture as a solution in the dry solvent.

The reaction suitably takes place in the absence of moisture and undernon-oxidising conditions, for example under a dry and non-oxidisingatmosphere. When gaseous hydrogen chloride is passed directly into thereaction mixture, the gas itself provides the necessary dry andnon-oxidising atmosphere. If the hydrogen chloride is added to thereaction mixture as a solution in the dry solvent, it may be desirableto use a suitable inert gas such as dry nitrogen to provide the dry andnon-oxidising atmosphere.

Preferably there is used a substantially stoichiometric proportion oftrialkylphosphite. The proportion of the acid will depend on theparticular acid used. If hydrochloric acid is used, there is preferablyemployed from 3 to 12 moles of hydrochloric acid per mole ofmethyleneaminoacetonitrile trimer.

It is a particular advantage of the process of the present inventionthat the product precipitates in a substantially pure form allowingready isolation.

Hydrolysis of the alkyl ester of N-phosphonomethyl-glycinonitrile toN-phosphonomethylglycine or a salt thereof is a well-known process andis described for example in U.S. Pat. No. 3,923,877.

The process of the present invention can be operated as either a batchor continuous or semi-continuous reaction and is particularly wellsuited to efficient commercial operation and in particular is wellsuited to integration with a subsequent reaction to formN-phosphonomethylglycine or a salt thereof.

In a typical process, the insoluble acid salt of the alkyl ester of N-phosphonomethylglycinonitrile is recovered from the reaction byfiltration whilst the reaction solvent is re-cycled, optionally with apurification stage. The acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile is then hydrolysed, for example bytreatment with aqueous hydrochloric acid, and N-phosphonomethylglycineis formed.

There are advantages for such a combined process in using a highertrialkylphosphite such as tributylphosphite or tripentylphosphite asphosphonating agent. In particular, the product of the hydrolysis of thebutyl or pentyl ester of N-phosphonomethylglycinonitrile is butanol orpentanol respectively. The higher alkanols are immiscible with theaqueous hydrolysis phase and the organic phase can be readily separatedand the alkanol re-cycled and used for the formation of more trialkylphosphite, for example by reaction with phosphorous trichloride.Furthermore, the butyl or pentyl chloride formed in the course of thereaction of the present invention (scheme 1) may conveniently be removedfrom the reaction solvent (filtrate) by distillation and added to thehydrolysis stage of the butyl or pentyl ester ofN-phosphonomethylglycinonitrile where it is itself hydrolysed to formfurther butanol or pentanol respectively which becomes included in there-cycle.

Thus according to a further aspect of the present invention there isprovided a process for the manufacture of N-phosphonomethylglycine whichcomprises

i) reacting methyleneaminoacetonitrile trimer with tributylphosphite ortripentylphosphite under anhydrous conditions and in the presence of ananhydrous acid and an inert solvent in which themethyleneaminoacetonitrile trimer starting material is at leastpartially soluble and the acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile product is substantially insoluble andthereafter;

ii) filtering the reaction mixture from stage (i) to recover theprecipitated acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile from the filtrate containing solvent andbutyl chloride or pentyl chloride;

iii) hydrolysing the acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile under acidic conditions to formN-phosphonomethylglycine and butanol or pentanol;

iv) distilling the filtrate from stage (ii) and re-cycling the solventto stage (i) and the butyl chloride or pentyl chloride to stage (iii)where it undergoes hydrolysis to form butanol or pentanol respectively;

v) recovering the butanol or pentanol from stage (iii) by phaseseparation, reacting it with phosphorous trichloride to formtributylphosphite and tripentylphosphite respectively and recycling thetributylphosphite or tripentylphoshite to stage (i); and

vi) recovering the N-phosphonomethylglycine product from stage (iii).

The N-phosphonomethylglycine product from stage (iii) is convenientlyrecovered by crystallisation.

The present invention is illustrated by the following Examples in whichall parts and percentages are by weight unless otherwise stated.

EXAMPLE 1

Methyleneaminoacetonitrile trimer 1.7 g (0.0083 g mol) andtrimethylphosphite 3.1 g (0.025 g mol) were suspended in 30 ml of ethylacetate. The mixture was stirred and maintained at about roomtemperature whilst anhydrous HCl was introduced slowly. During theaddition, a white precipitate was formed. GC analysis showed that allthe trimer had been consumed after the reaction had been allowed tostand overnight at ambient temperature. The solid was then isolated byfiltration and washed with solvent. 3.6 g of product were obtained,corresponding to a 67% yield. The solid was analysed by GC and NMR andwas found to be the hydrochloride salt of the dimethyl ester ofphosphonomethylglycinonitrile. The product was essentially pure with nosignificant contaminants identified by GC or NMR.

EXAMPLE 2

The procedure of Example 1 was repeated except that acetonitrile wasused as solvent. 3.1 g of essentially pure dimethyl ester ofphosphonomethylglycinonitrile was obtained, corresponding to a yield of56%.

EXAMPLE 3

The procedure of Example 2 was repeated except that 1.825 g (0.05 g mol)of anhydrous HCl was dissolved in 30 ml of acetonitrile prior toaddition to the reaction vessel. 3.4 g of essentially pure dimethylester of phosphonomethylglycinonitrile was obtained, corresponding to ayield of 63%.

EXAMPLE 4

Methyleneaminoacetonitrile trimer 1.7 g and trimethylphosphite 3.2 gwere suspened in 40 ml of dichloromethane. The mixture was stirred andmaintained at a temperature below 35° C. whilst anhydrous HCl wasintroduced over a period of 2 hours. During the addition, a whiteprecipitate was formed. After cooling to 0° C., the product wasfiltered, washed with 20 ml chilled dichloromethane and dried to give2.9 g of the dimethyl ester of phophonomethylglycinonitrile (54.1%yield). Proton nmr indicated that the product was essentially pure.

EXAMPLE 5

Methyleneaminoacetonitrile trimer 3.4 g and tributylphosphite (14 g of90% strength) were dissolved in 40 ml of acetonitrile. The mixture wasstirred and maintained at a temperature below 35° C. whilst anhydrousHCl was introduced over a period of 3 hours at a rate of 30 ml/min.During the addition, a white precipitate was formed. After cooling to 0°C., the product was filtered, washed with chilled acetonitrile and driedto give 13.2 g of the dibutyl ester of phophonomethylglycinonitrile (88%yield). Proton nmr indicated that the product was essentially pure.

EXAMPLE 6

The procedure of Example 5 was repeated except that ethyl acetate wasused in place of acetonitrile. The methyleneaminoacetonitrile was onlypartially soluble in the ethyl acetate and was suspended in the reactinmixture. 11.9 g of essentially pure dibutyl ester ofphosphonomethylglycinonitrile (79.7% yield) were obtained. ##STR1##

I claim:
 1. A process for the manufacture of an acid salt of an alkylester of N-phosphonomethylglycinonitrile which comprises reactingmethyleneaminoacetonitrile trimer with a trialkylphosphite underanhydrous conditions and in the presence of an anhydrous acid and aninert solvent in which the methyleneaminoacetonitrile trimer startingmaterial is at least partially soluble and the acid salt of the alkylester of N-phosphonomethylglycinonitrile product is substantiallyinsoluble and thereafter recovering the precipitated acid salt of thealkyl ester of N-phosphonomethylglycinonitrile.
 2. A process accordingto claim 1 wherein the trialkylphosphite is a tri(C₁₋₇ alkyl)phosphite.3. A process according to claim 2 wherein the trialkylphosphite is a tri(C₁₋₅ alkyl)phosphite.
 4. A process according to any of the precedingclaims wherein the anhydrous acid is hydrogen chloride.
 5. A processaccording to claim 4 wherein there is used a substantiallystoichiometric proportion of trialkylphosphite and from 3 to 12 moles ofhydrochloric acid per mole of methyleneaminoacetonitrile trimer.
 6. Aprocess according to claim 1 wherein the inert solvent is a nitrile, anester, a haloalkane, a ketone, an ether or a halogenated aromatichydrocarbon.
 7. A process according to claim 5 wherein the inert solventis acetonitrile, ethyl acetate, methyl isobutyl ketone, diethyl ether,tetrahydrofuran, ethylene dichloride, dichloromethane ormonochlorobenzene.
 8. A process according to claim 1 wherein thereaction takes place at a temperature of from -10° C. to 50° C.
 9. Aprocess for the manufacture of N-phosphonomethylglycine which comprisesi) reacting methyleneaminoacetonitrile trimer with a trialkylphosphiteunder anhydrous conditions and in the presence of an anhydrous acid andan inert solvent in which the methyleneaminoacetonitrile trimer startingmaterial is at least partially soluble and the acid salt of the alkylester of N-phosphonomethylglycinonitrile product is substantiallyinsoluble and thereafterii) recovering the precipitated acid salt of thealkyl ester of N-phosphonomethylglycinonitrile and iii) hydrolysing theacid salt of the alkyl ester of N-phosphonomethylglycinonitrile to formN-phosphonomethylglycine.
 10. A process for the manufacture ofN-phosphonomethylglycine which comprisesi) reactingmethyleneaminoacetonitrile trimer with tributylphosphite ortripentylphosphite under anhydrous conditions and in the presence of ananhydrous acid and an inert solvent in which themethyleneaminoacetonitrile trimer starting material is at leastpartially soluble and the acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile product is substantially insoluble andthereafter; ii) filtering the reaction mixture from stage (i) to recoverthe precipitated acid salt of the alkyl ester ofN-phosphonomethylglycinonitrile from the filtrate containing solvent andbutyl chloride or pentyl chloride; iii) hydrolysing the acid salt of thealkyl ester of N-phosphonomethylglycinonitrile under acidic conditionsto form N-phosphonomethylglycine and butanol or pentanol; iv) distillingthe filtrate from stage (ii) and re-cycling the solvent to stage (i) andthe butyl chloride or pentyl chloride to stage (iii) where it undergoeshydrolysis to form butanol or pentanol respectively; v) recovering thebutanol or pentanol from stage (iii) by phase separation, reacting itwith phosphorous trichloride to form tributylphosphite andtripentylphosphite respectively and recycling cycling thetributylphosphite or tripentylphoshite to stage (i); and vi) recoveringthe N-phosphonomethylglycine product from stage (iii).